US2025082629A1PendingUtilityA1
Antiproliferative compounds and second active agents for combined use
Est. expiryJan 9, 2039(~12.5 yrs left)· nominal 20-yr term from priority
Inventors:Lilly L. Wong
A61K 45/06A61K 31/706A61K 31/69A61K 31/573A61K 31/551A61K 31/52A61K 31/519A61K 31/517A61K 31/506A61K 31/5025A61K 31/4985A61K 31/497A61K 31/454A61K 31/444A61K 31/436A61P 35/00A61K 2300/00A61K 31/4545A61K 31/5377A61K 31/4184A61K 31/4523A61K 31/7076A61K 31/5517A61K 31/4704A61K 31/4188A61K 31/4178A61K 31/416A61K 31/496A61P 7/00
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Claims
Abstract
Provided herein are methods of using 4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile, or an enantiomer, a mixture of enantiomers, a tautomer, or a pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing multiple myeloma. The second active agent is one or more of a BTK inhibitor, an mTOR inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an MEK inhibitor, an XPO1 inhibitor, a DOT1L inhibitor, an EZH2 inhibitor, a JAK2 inhibitor, a BRD4 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an AURKB inhibitor, a BIRC5 inhibitor, a BET inhibitor, or a DNA methyltransferase inhibitor.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of treating multiple myeloma comprising administering to a patient in need thereof a therapeutically effective amount of a compound in combination with a second active agent, wherein the compound is Compound 1 of formula
or an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof; and wherein the second active agent is one or more of a BTK inhibitor, an mTOR inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an MEK inhibitor, an XPO1 inhibitor, a DOT1L inhibitor, an EZH2 inhibitor, a JAK2 inhibitor, a BRD4 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an AURKB inhibitor, a BIRC5 inhibitor, a BET inhibitor, or a DNA methyltransferase inhibitor.
2 . A method of treating multiple myeloma comprising administering to a patient in need thereof a therapeutically effective amount of a compound in combination with a second active agent, wherein the compound is Compound 2 of formula
or a tautomer, isotopolog, or pharmaceutically acceptable salt thereof; and wherein the second active agent is one or more of a BTK inhibitor, an mTOR inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an MEK inhibitor, an XPO1 inhibitor, a DOT1L inhibitor, an EZH2 inhibitor, a JAK2 inhibitor, a BRD4 inhibitor, a PLK1 inhibitor, an NEK2 inhibitor, an AURKB inhibitor, a BIRC5 inhibitor, a BET inhibitor, or a DNA methyltransferase inhibitor.
3 . The method of claim 2 , wherein the compound is Compound 2.
4 . The method of any one of claims 1 to 3 , wherein the second active agent is a BTK inhibitor.
5 . The method of claim 4 , wherein the BTK inhibitor is ibrutinib, or acalabrutinib, or a stereoisomer, mixture of stereoisomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof.
6 . The method of claim 5 , wherein the BTK inhibitor is ibrutinib.
7 . The method of any one of claims 1 to 3 , wherein the second active agent is an mTOR inhibitor.
8 . The method of claim 7 , wherein the mTOR inhibitor is rapamycin or an analog thereof (also termed rapalog).
9 . The method of claim 8 , wherein the mTOR inhibitor is everolimus.
10 . The method of any one of claims 1 to 3 , wherein the second active agent is a PIM inhibitor.
11 . The method of claim 10 , wherein the PIM inhibitor is LGH-447, AZD1208, SGI-1776, or TP-3654, or a stereoisomer, mixture of stereoisomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof.
12 . The method of claim 11 , wherein the PIM inhibitor is LGH-447 or a hydrochloride salt of LGH-447.
13 . The method of any one of claims 1 to 3 , wherein the second active agent is an IGF-1R inhibitor.
14 . The method of claim 13 , wherein the IGF-1R inhibitor is linsitinib.
15 . The method of any one of claims 1 to 3 , wherein the second active agent is an MEK inhibitor.
16 . The method of claim 15 , wherein the MEK inhibitor is trametinib, trametinib dimethyl sulfoxide, cobimetinib, binimetinib, or selumetinib, or a stereoisomer, mixture of stereoisomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof.
17 . The method of claim 16 , wherein the MEK inhibitor is trametinib or trametinib dimethyl sulfoxide.
18 . The method of any one of claims 1 to 3 , wherein the second active agent is an XPO1 inhibitor.
19 . The method of claim 18 , wherein the XPO1 inhibitor is selinexor.
20 . The method of any one of claims 1 to 3 , wherein the second active agent is a DOT1L inhibitor.
21 . The method of claim 20 , wherein the DOT1L inhibitor is SGC0946, or pinometostat, or a stereoisomer, mixture of stereoisomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof.
22 . The method of claim 21 , wherein the DOT1L inhibitor is SGC0946.
23 . The method of claim 21 , wherein the DOT1L inhibitor is pinometostat.
24 . The method of any one of claims 1 to 3 , wherein the second active agent is an EZH2 inhibitor.
25 . The method of claim 24 , wherein the EZH2 inhibitor is tazemetostat, 3-deazaneplanocin A (DZNep), EPZ005687, EI1, GSK126, UNC1999, CPI-1205, or sinefungin, or a stereoisomer, mixture of stereoisomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof.
26 . The method of claim 25 , wherein the EZH2 inhibitor is tazemetostat.
27 . The method of claim 25 , wherein the EZH2 inhibitor is UNC1999.
28 . The method of claim 25 , wherein the EZH2 inhibitor is CPI-1205.
29 . The method of any one of claims 1 to 3 , wherein the second active agent is a JAK2 inhibitor.
30 . The method of claim 29 , wherein the JAK2 inhibitor is fedratinib, ruxolitinib, baricitinib, gandotinib, lestaurtinib, momelotinib, or pacritinib, or a stereoisomer, mixture of stereoisomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof.
31 . The method of claim 30 , wherein the JAK2 inhibitor is fedratinib.
32 . The method of any one of claims 1 to 3 , wherein the second active agent is a BRD4 inhibitor.
33 . The method of claim 32 , wherein the BRD4 inhibitor is JQ1.
34 . The method of any one of claims 1 to 3 , wherein the second active agent is a PLK1 inhibitor.
35 . The method of claim 34 , wherein the PLK1 inhibitor is BI2536.
36 . The method of any one of claims 1 to 3 , wherein the second active agent is an NEK2 inhibitor.
37 . The method of claim 36 , wherein the NEK2 inhibitor is JH295.
38 . The method of any one of claims 1 to 3 , wherein the second active agent is an AURKB inhibitor.
39 . The method of claim 38 , wherein the AURKB inhibitor is barasertib or AZD1152-HQPA.
40 . The method of any one of claims 1 to 3 , wherein the second active agent is a BIRC5 inhibitor.
41 . The method of claim 40 , wherein the BIRC5 inhibitor is YM155.
42 . The method of any one of claims 1 to 3 , wherein the second active agent is a BET inhibitor.
43 . The method of claim 42 , wherein the BET inhibitor is birabresib or Compound C (4-[2-(cyclopropylmethoxy)-5-(methanesulfonyl)phenyl]-2-methylisoquinolin-1 (2H)-one), or a stereoisomer, mixture of stereoisomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof.
44 . The method of any one of claims 1 to 3 , wherein the second active agent is a DNA methyltransferase inhibitor.
45 . The method of claim 44 , wherein the DNA methyltransferase inhibitor is azacitidine.
46 . The method of any one of claims 1 to 45 , wherein the multiple myeloma is relapsed, refractory or resistant.
47 . The method of claim 46 , wherein the multiple myeloma is refractory or resistant to lenalidomide.
48 . The method of claim 46 , wherein the multiple myeloma is refractory or resistant to pomalidomide.
49 . The method of any one of claims 1 to 45 , wherein the multiple myeloma is newly diagnosed multiple myeloma.
50 . The method of any one of claims 1 to 49 , additionally comprising administering to the patient an additional active agent.
51 . The method of claim 50 , wherein the additional active agent is dexamethasone.
52 . The method of claim 50 , wherein the additional active agent is bortezomib.Join the waitlist — get patent alerts
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